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Keywords: Decision Support System, Inappropriateness, Health Information Technology, Knowledge Management Diagnosis (δια-γνοσισ from ancient Greek: "δια" through the, "γνοσισ" knowledge) allows identifying the nature and location of a disease through the awareness of symptoms and signs. A diagnosis should be the result produced by listening, observing and studying the patient. This process utilizes devices such as history and semiotics, which are flanked by laboratory tests that, as other techniques such as medical imaging, can be considered the technological extension of the senses of the physician. Knowledge is the faculty that allows conscious decisions within the diagnostic process and that leads the subsequent actions on the patient [1, 2]. Laboratory tests have taken a leading role as diagnostic decision aids, having been estimated that the Laboratory Medicine influences 60-70% the diagnosis [3]. This leading role is confirmed, for example, by the data of the Veneto Region (about 5 million inhabitants), showing that in public health structures more than 70 million tests/year, for a value of about 322 million euros, are carried out [2]. The budget of Laboratory Medicine in Italy is only 2% of the total health care cost, which is anyway relevant. On the other hand, the utility of diagnostic tests is affected by a significant proportion of inappropriateness [5]. A literature estimates the phenomenon of over-and underutilization between 10-50% of the total demand [6-21]. Despite the difficulty to evaluate objectively the appropriateness [22], the feeling of its relevance among professionals is, in any case, widespread, especially with regard to the excessive demand, even if there are data that prove an underestimation of the potentialities of the laboratory [23]. The source of the problem may essentially come from three causes: a) the low cost of laboratory tests (account as "little ticket technologies") could lead physicians to think that these benefits cannot be denied to the patient. This fact together with the facility of access (usually without reservation and waiting times), may contribute to make the laboratory performance too easily available; b) defensive medicine may persuade the physician to prescribe tests in order to avoid the charge of not doing everything possible; c) slow response time to the innovation mainly due to the difficulty of transmission and consolidation of knowledge. In fact, even decades can pass from the evidence of the usefulness or uselessness of a test to the concrete change in the prescriptive act [24-27]. This is a critical issue not only in the diffusion of new knowledge, but also in the use of tests that may be defined historical [28]. The knowledge is the intellectual tool of decision that manages not only the quality of the tests (usefulness of tests, strategies proposed by prescriptive guidelines, sensitivity, specificity, predictive value, technical features, legislation, and costs), but also and above all, the quantity of needed tests. The main critical issue that affects the knowledge lies in the fact that if the first edition of Merck's Manual of 1899 [29] listed 13 tests easily memorized, the tests available today are more than 500 and therefore over the human cognitive ability [30]. In this paper we present an innovative informatics solution, integrated to clinical processes, in order to change the clinical approach to laboratory tests and, that can be a tool for improving knowledge. The percentages of inappropriateness mentioned above, are the main indicators of lack of efficacy of the strategies used up to now (guidelines, protocols and flow charts, conventions, treaties, consensus conferences, agreements between colleagues). The same have also proved not to be adequate to affect permanently and quickly on behavioral change. We think crucial to apply structural instruments for the transmission of scientific information in order to allow: a) the continuing education in order to decrease the response time to innovation, b) the consolidation of the state of the art, c) the improvement of the transmission of knowledge, in order to overcome the criticality of clinical staff turnover, d) the homogeneity of behavior. We believe that such targets could be achieved through a strategic communication [31] using a Decision Support System (DSS), to promote virtuous behavior of physicians in the act of prescription. The indications provided were collected in a handbook for the correct prescription of both traditional and innovative tests and particularly in the fields of molecular biology, genomics, proteomics and epigenetics. The Health Information Technology (HIT) makes it possible to test solutions that will make the information accredited, updated and available on the point of care, so that prescribers can adopt the most appropriate, synthetic, and cost effective choices [32- 36]. On the other hand, the literature shows that the use of a DSS improves significantly the performance of the physician and besides that, the attitude of General Practitioners (GPs) in respect of a DSS is good [37]. As regards the economic issue, the same in only a few studies has been exhaustively analyzed [38 - 41]. The way ahead is to adopt the indications generated by a consensus among peers and in agreement with the guidelines. Finally the idea has been to provide physicians with a list of indications updatable in real time and extensible progressively to most laboratory tests. The continuous updating through the information network would solve one of the main problems in the management of appropriateness. In fact, the judgment of appropriateness is often not a final choice, but is a developmental continuity linked to technological progress and scientific knowledge, and also to the cost/benefit. Connectivity should be the tool to define an explicit hierarchy and updated solutions, in which context the responsibility of prescribers might develop [42]. The aim of this paper is to illustrate the characteristics of a DSS and to present the results of two trials conducted in two Italian Health Care Authorities (Veneto Region). The objective of the trials was twofold: a) assessment of the technical feasibility of the software tool in terms of ease of use, while checking if the same software presented some sort of conflicts with the application programs of the General Practitioners (GPs); b) determining whether the use of the DSS could induce a change in prescribing behavior.